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An epigenetic circuit controls neurogenic programs during neocortex development
- Source :
- Development. 148
- Publication Year :
- 2021
- Publisher :
- The Company of Biologists, 2021.
-
Abstract
- The production and expansion of intermediate progenitors (IPs) are essential for neocortical neurogenesis during development and over evolution. Here, we have characterized an epigenetic circuit that precisely controls neurogenic programs, particularly properties of IPs, during neocortical development. The circuit comprises a long non-coding RNA (LncBAR) and the BAF (SWI/SNF) chromatin-remodeling complex, which transcriptionally maintains the expression of Zbtb20. LncBAR knockout neocortex contains more deep-layer but fewer upper-layer projection neurons. Intriguingly, loss of LncBAR promotes IP production, but paradoxically prolongs the duration of the cell cycle of IPs during mid-later neocortical neurogenesis. Moreover, in LncBAR knockout mice, depletion of the neural progenitor pool at embryonic stage results in fewer adult neural progenitor cells in the subventricular zone of lateral ventricles, leading to a failure in adult neurogenesis to replenish the olfactory bulb. LncBAR binds to BRG1, the core enzymatic component of the BAF chromatin-remodeling complex. LncBAR depletion enhances association of BRG1 with the genomic locus of, and suppresses the expression of, Zbtb20, a transcription factor gene known to regulate both embryonic and adult neurogenesis. ZBTB20 overexpression in LncBAR-knockout neural precursors reverses compromised cell cycle progressions of IPs.
- Subjects :
- Mice, Knockout
Neurons
Neocortex
Neurogenesis
Cell Cycle
Embryonic Development
Biology
Chromatin Assembly and Disassembly
Epigenesis, Genetic
Mice
medicine.anatomical_structure
Neural Stem Cells
medicine
Animals
RNA, Long Noncoding
Epigenetics
Neuroglia
Molecular Biology
Neuroscience
Transcription Factors
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 148
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....7d1e110bdae66af33e50d190cbee20cb